Tangential-flow filtration system

ABSTRACT

The present invention includes a system and method for transferring a selected solute species from a fluid mixture to a fluid media. The system of the present invention includes a convergent channel for passing a fluid mixture containing a selected species tangentially across the first surface of a porous membrane. A fluid media is directed to flow tangentially over the second surface of the membrane. As the fluid mixture and the fluid media flow on opposite sides of the membrane, the selected species traverses the membrane leaving the fluid mixture and entering the fluid media. The volumetric loss to the fluid mixture associated with the loss of the selected species is compensated for by the convergency of the channel. As a result a constant velocity is maintained over the membrane, maximizing the selectivity of the filtration process.

RELATED APPLICATION

[0001] This application claims the benefit of U.S. provisionalapplication No. 60/Unassigned, (Our Docket No.: PRO984) having aneffective filing date of Jan. 17, 1996, as per the Petition forConversion dated Dec. 5, 1996 under 37 CFR 1.53(b)(2)(ii) from U.S. Ser.No. 08/587,644, filed Jan. 17, 1996, the contents of which areincorporated herein by reference.

FIELD OF THE INVENTION

[0002] The present invention pertains generally to filters which areuseful in isolating selected species from fluid mixtures. Morespecifically, the present invention pertains to tangential-flow filtersallowing high protein resolution. The present invention is particularly,but not exclusively, useful as a tangential-flow filter forultrafiltration of various biological media.

BACKGROUND OF THE INVENTION

[0003] In the past, a large number of varying techniques have beendeveloped for the filtration of fluid mixtures. Many of these techniquesrequire passing the fluid mixture through a membrane filter. In general,these membrane filtration techniques may be divided into three basiccategories based on filter pore size and filtration pressure. The firstof these categories, known as microfiltration, refers to filters havingrelatively large pore sizes and relatively low operating pressures. Thesecond category, ultrafiltration, refers to filters having intermediatepore sizes and intermediate operating pressures. Finally, the thirdcategory, reverse osmosis, refers to filters having extremely small poresizes and relatively high operating pressures. Predictably,microfiltration techniques are utilized when large solutes, or species,are to be filtered. Ultrafiltration is used when intermediate speciesare to be processed, and reverse osmosis is utilized when extremelysmall species are targeted.

[0004] Traditionally, membrane filters have functioned by placing aporous membrane perpendicularly across the path of a fluid mixture fromwhich a selected species is to be filtered. The fluid mixture flowsthrough the membrane and the selected species is retained by themembrane. A problem generally associated with traditional filtrationtechniques is tendency of the filter to accumulate solutes from thefluid mixture that is being filtered. Accumulation of these solutescreates a layer of solutes on the filtration membrane and has a tendencyto block, or clog, the pores of the membrane decreasing the flow of thefluid mixture, or flux, through the filtration membrane

[0005] The decrease in flux attributable to the accumulation of thesolute layer on the filtration membrane may be partially overcome byincreasing the pressure differential, or transmembrane pressure thatexists across the filtration membrane. Pressure increases of this typeare, however, limited in their effectiveness by the tendency of thefilter to become increasingly clogged as the filtration processcontinues. Eventually, of course, further pressure increases becomeimpractical and the filtration process must be halted and the cloggedmembrane replaced. This is especially true when biological or otherpressure sensitive species are being extracted.

[0006] A second problem associated with the accumulation of solutes onthe filtration membrane is the tendency for the solute layer to act as asecondary filter. As a result, as the layer of solutes deposited on thefiltration membrane increases, passage through the filtration membranebecomes limited to smaller and smaller solutes. The tendency for thesolute layer to act as a secondary filter is especially problematicbecause, unlike the decreased flux attributable to the same layer, itcannot be overcome by increasing the transmembrane pressure.

[0007] One solution to the problem of membrane blockage has been thedevelopment of tangential-flow filters. Filters of this type employ amembrane which is generally similar to the membrane types employed bytraditional filters In tangential-flow filters, however, the membrane isplaced tangentially to the flow of the fluid mixture to cause the fluidmixture to flow tangentially over a first side of the membrane. At thesame time, a fluid media is placed in contact with a second surface ofthe membrane. The fluid mixture and the fluid media are maintained underpressures which differ from each other. The resulting pressuredifferential, or transmembrane pressure, causes fluid within the fluidmixture, and species within the fluid mixture, to traverse the membrane,leaving the fluid mixture and joining the fluid media.

[0008] In operation, the tangential-flow of the fluid mixture over themembrane functions to prevent solutes within the fluid mixture fromsettling on the membrane surface. As a result, the use oftangential-flow filtration has proven to be an effective means ofreducing membrane blockage for membrane filters. Not surprisingly, then,a wide variety of differing designs exist for filters of thetangential-flow type. Unfortunately, even when tangential flowfiltration is used, there is still some tendency for solutes toaccumulate near the filtration membrane. As is the case with dead-endfilters, the accumulation of solutes degrades the filtration process,increases the transmembrane pressure and has the twin effects ofdecreasing the flux of solutes through the membrane and limitingtraversal through the membrane to smaller solutes. These problems areparticularly acute when the species of interest and other, non-desiredspecies within the fluid mixture have similar molecular weights, as isoften the case when mixtures of proteins are to be fractionated. As aresult, tangential flow filtration techniques are generally employedonly where the species of interest and the non-desired species havemolecular weights which differ by a factor of at least ten.

[0009] A tangential flow filtration which optimizes the soluteconcentration at the filtration membrane to increase the ability of thefilter to select between similarly sized species is disclosed in U.S.Pat. No 5,256,294 entitled “Tangential Flow Filtration Process andApparatus” which issued to van Reis and is assigned to the same assigneeas the present invention. For the device disclosed by van Reis, thetransmembrane pressure of the filtration process is maintained at alevel which is generally less than the transmembrane pressure used intraditional tangential flow filtration systems. More specifically, ithas been observed that flux in tangential flow filtration systemsincreases as a function of transmembrane pressure until thetransmembrane pressure reaches a transition point pressure or TPP Oncethe transmembrane pressure reaches TPP, flux is relatively independentof further increases in the transmembrane pressure. Traditionaltangential flow filtration systems have operated with transmembranepressure which generally equal or exceed TPP. In comparison, the devicedisclosed by van Reis maintains the transmembrane pressure of thefiltration pressure at a value which is less than TPP. As a result, fluxthrough the device of van Reis may be less than the flux achieved bytraditional tangential flow filtration systems. At the same time,however, the ability of the filter to select between similarly sizedspecies is enhanced.

[0010] In spite of the development of tangential flow filtration systemsand improved tangential flow filtration systems, such as the filtrationsystem disclosed by van Reis, there is a continual need for improvedfiltration systems. In particular, there exists a need for filtrationsystems with enhanced abilities to select between similarly sizedsolutes, such as when mixtures of proteins are to be fractionated. Inlight of the above, it is an object of the present invention to providea tangential-flow filtration system for removing solute species from afluid mixture. Yet another object of the present invention is to providea tangential-flow filtration system with an enhanced ability to selectbetween similarly size solutes. Yet another object of the presentinvention is to provide a tangential-flow filtration system which isparticularly suitable for the filtration of protein mixtures. Stillanother object of the present invention is to provide a tangential-flowfiltration system which is relatively simple to use, easy to manufactureand comparatively cost effective.

SUMMARY OF THE PREFERRED EMBODIMENTS

[0011] The present invention includes a method and system fortransferring a selected solute species from a fluid mixture to a fluidmedia. The system of the present invention includes a filtrationmembrane preferably formed as a flat, elongated, sheet having a firstsurface and a second surface. The filtration membrane has a preferredpore size chosen to allow the selected solute species to traverse themembrane. At the same time, the pore size prevents the passage ofsolutes that exceed the size of the selected species.

[0012] The system of the present invention also includes a first channeland a second channel. Both the first channel and the second channel areconstructed to allow fluid to flow tangentially across a surface of thefiltration membrane. More specifically, the first channel is constructedwith an input port and an output port. Fluid, such as the fluid mixture,may enter the first channel at the input port. Between the input portand the output port, the fluid mixture flows tangentially across thefirst surface of the membrane. The fluid mixture then leaves the firstchannel at the output port Similarly, the second channel is constructedwith an input port and an output port. Fluid media supplied at the inputport of the second channel flows tangentially across the second surfaceof the filtration membrane before exiting the second channel at theoutput port. Effectively, as a structural result of the first and secondchannels, an arrangement is created whereby the fluid mixture and fluidmedia flow tangentially on opposite sides of the filtration membrane.Generally, the first and second channels may be formed as part of asingle cassette which also maintains the position of the filtrationmembrane.

[0013] The present invention also includes a system of pumps connectedto the first and second channels. Functionally, the pumping systemallows the fluid mixture and the fluid media to be passed through thefirst and second channels. Additionally, the pumping system allows thevelocity in the first and second channels to be selectively controlled.By selectively controlling the velocities in the first and secondchannels, and by controlling outlet pressures, a pressure differential,or transmembrane pressure, is created over the membrane between thefluid mixture in the first channel and the fluid media in the secondchannel.

[0014] For the purposes of the present invention, numerous types offluid pumps are adaptable for use in the pumping system. In fact, it maybe appreciated that almost any pump that provides the required abilitiesto move the fluid mixture and fluid media and to control the pressurewithin the first and second channels may be employed. In practice,however, it will generally be the case that the specific pump typechosen will depend largely on the requirements of the specific filteringoperation.

[0015] As described in the preceding paragraphs, the present inventionincludes a pumping system that is used to pass a fluid mixture and afluid media over opposite surfaces of a porous membrane. The passing ofthe fluid mixture and the fluid media over opposite sides of themembrane is performed under pressure and causes the selected species inthe fluid mixture to traverse the filtration membrane, leaving the fluidmixture and joining the fluid media. Preferably, the pressure of thefluid mixture in the first channel and the pressure of the fluid mediain the second channel are controlled to create a transmembrane pressurewhich is less than the transition point pressure (TPP) of the filtrationprocess.

[0016] Importantly, for the purposes of the present invention, the firstchannel is constructed to be convergent in the direction of the flow ofthe fluid mixture. Alternatively stated, the first channel ischaracterized by a cross-sectional area which decreases in the directionof the flow of the fluid mixture. As a result, the geometry of the firstchannel effectively compensates for the decreasing volume of the fluidmixture caused by the traversal of the filtration membrane by theselected species. More importantly, however, by compensating for thevolumetric change of the fluid mixture, the convergent geometryestablishes a nearly constant rate of flow for the fluid mixturethroughout the first channel. The constant velocity of the fluid mixturethroughout the first channel optimizes the ability of the filtrationmembrane to select between similarly sized solute species.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The novel features of this invention, as well as the inventionitself, both as to its structure and its operation, will be bestunderstood from the accompanying drawings, taken in conjunction with theaccompanying description, in which similar reference characters refer tosimilar parts, and in which:

[0018]FIG. 1 is a schematic diagram of the filtration system of thepresent invention;

[0019]FIG. 2 is a schematic diagram of an alternate embodiment of thefiltration system of the present invention;

[0020]FIG. 3 is a schematic diagram of the filtration system of thepresent invention, shown in a cascaded configuration; and

[0021]FIGS. 4 and 5 are schematic diagrams of the filtration system ofthe present invention, shown in multi-channel configurations.

DESCRIPTION OF THE PREFERRED EMBODIMENT

[0022] The present invention includes a method and system fortransferring a selected solute species from a fluid mixture to a fluidmedia. The filtration system of the present invention is shown in FIG. 1and generally designated 10. In FIG. 1, it may be seen that the system10 includes a first channel 12 and a second channel 14. The firstchannel 12 has an input end 16 and an output end 18. The first channel12 is characterized by an overall length 20. Additionally, the firstchannel 12 may be seen to have an initial cross-sectional area 22measured at the input end 16 and a final cross-sectional area 24measured at the output end 18. Importantly, for purposes of the presentinvention, the initial cross-sectional area 22 exceeds the finalcross-sectional area 24 giving the first channel 12 a narrowing, orconverging, quality over length 20. Like the first channel 12, thesecond channel 14 has an input end 26 and an output end 28.

[0023] Continuing with FIG. 1, it may be seen that a filtration membrane30 is positioned between, and separates, the first channel 12 and thesecond channel 14. The filtration membrane has a first surface 32 and asecond surface 34. For the purposes of the present invention, thefiltration membrane 30 has a porous quality and, preferably, ischaracterized by a uniform pore size. The specific material and thespecific pore size chosen for the filtration membrane 30 depends on thesize of the solute species that will be removed by the filtration system10. In general, many configurations are possible for first channel 12and second 14. For example, as shown in FIG. 1, for the preferredembodiment of the present invention, the first channel 12 and the secondchannel 14 are configured in a side-by-side relationship. Alternatively,the first channel 12 and second channel 14 may be configured to becoaxially disposed with either the first channel 12 or second channel 14positioned inside of the other. In fact, any configuration of the firstchannel 12 and second channel 14 that forces the fluid mixture and fluidmedia to flow tangentially over opposite sides of a filtration membraneand provides the required convergent configuration for the first channel12 may be adapted for use in the present invention.

[0024] The present invention may also include a feed pump 36 and valve38. The feed pump 36 is connected to an input conduit 40 which connects,in turn to the input end 16 of the first channel 12. For the purposes ofthe present invention, numerous types of fluid pumps are adaptable foruse as feed pump 36. In fact, it may be appreciated that almost any pumptype that provides the required abilities to move the fluid mixture andcontrol the pressure within the first channel 12 may be employed.Functionally, the feed pump 36 causes the fluid mixture to pass throughthe input conduit 40 and into the input end 16 of the first channel 12.Once in the first channel 12, the fluid mixture passes along the length20 of the first channel 12 in the direction of the arrow 42. A mixtureoutput conduit 44 is connected at the output end of the first channel 12providing a path for removal of the fluid mixture from the first channel12.

[0025] A recirculating pump 46 is also included in the presentinvention. The recirculating pump 46 is attached to a recirculationconduit 48 which is connected, in turn, to the input end 26 of thesecond channel 14. ,The recirculating pump 46 is also connected to areturn conduit 50 which is connected, in turn, to the output end 28 ofthe second channel 14. As may be appreciated by reference to FIG. 1,operation of the recirculating pump 46 forces a stream of fluid mediathrough the recirculation conduit 48 and into the second channel 14. Thefluid media flows through the second channel 14 in the directionindicated by the arrow 52. The fluid media then enters the returnconduit 50 at the output end 28 of the second channel 14. The returnconduit 50 then conveys the fluid media back to the recirculating pump46.

[0026] As described in the preceding paragraph, the recirculating pump46, recirculation conduit 48, second channel 14 and return conduit 50form a circuit through which fluid media may be continuously circulated.To add or subtract fluid media from the system 10, an extraction pump54, or valve 56, are connected to a media output conduit 58.

OPERATION

[0027] In operation of the present invention, feed pump 36 is used topass a fluid mixture containing a selected solute species to be filteredthrough input conduit 40 and into first channel 12. The fluid mixturepasses through first channel 12 in the direction indicated by arrow 42.Within the first 20 channel 12, the fluid mixture passes tangentiallyover the first surface 32 of the filtration membrane 30. As the fluidmixture passes through first channel 12, the feed pump 36 and valve 38maintains the fluid mixture at a predetermined operational pressure.After flowing the length 20 of the first channel 12, the fluid mixtureexits the first channel 12 through the mixture output conduit 44. Forthe purposes of the present invention, processing of the fluid mixturemay proceed as a batch or continuous process. In cases where acontinuous process is to be utilized, the system 10 shown in FIG. 1 isused to pass the fluid mixture through the first channel 12 asdescribed. In cases where a batch process is to be used, however, thefluid mixture must be forced to repeatedly flow through the firstchannel 12. In such cases, the system of FIG. 1 may be reconfigured toestablish a connection between the mixture output conduit 44 and thefeed pump 36.

[0028] As the feed pump 36 is causing the fluid mixture to flow throughthe first channel 12, a fluid media is being recirculated in the secondchannel 14. More specifically, the recirculating pump 46 simultaneouslywithdraws fluid media from the return conduit 50 and passes fluid to therecirculation conduit 48. As a result, fluid media is withdrawn from theoutput end of 28 of the second channel 14 and added at the input end 26of the second channel 14. The overall result is that the fluid mediaflows through the second channel 14 in the direction of the arrow 52.Within the second channel 14, the fluid mixture passes tangentially overthe second surface 34 of the filtration membrane 30 As the fluid masspasses through second channel 14, the recirculating pump 46, extractionpump 54 or valve 56 maintain the fluid media at a predeterminedoperational pressure. As a result of the predetermined operationalpressure within the first channel 12 and the predetermined operationalpressure within the second channel 14, a pressure differential, ortransmembrane pressure, is applied across the filtration membrane 30.For the purposes of the present invention, the transmembrane pressure ofthe filtration process is maintained at a value that lies between fiveand one-hundred percent (5-100%) of the transition point pressure (TPP)of the filtration process, where TPP is defined as a pressure abovewhich flux through the filtration membrane 30 is no longer dependent onthe transmembrane pressure.

[0029] As the fluid mixture and fluid media flow on opposite sides ofthe filtration membrane 30, the selected solute species traverses thefiltration membrane 30, leaving the fluid mixture and joining the fluidmedia. The rate at which the selected species traverses the filtrationmembrane 30 is dependent on a number of factors. These factors include:the particular species, the constituents of the fluid mixture and fluidmedia, the flow rate of the fluid mixture and fluid media, the physicalcharacteristics of the filtration membrane 30, the pressure in the firstchannel 12 and the second channel 14, and the temperature of the fluidmixture and fluid media.

[0030] As the selected species traverses the filtration membrane 30, thevolume occupied by the fluid mixture is effectively decreased.Importantly, in the present invention, the loss of volume of the fluidmixture within the first channel 12 is matched by the convergentgeometry of the first channel 12. More specifically, for the presentinvention, the initial cross-section 22, final cross-section 24 andlength 20 of the first channel 12 are chosen to produce an overallgeometry for the first channel 12 which compensates for the loss of thefluid volume of the fluid mixture due to traversal of the selectedspecies through the filtration membrane 30. By compensating for the lossof the selected species, the velocity at which the fluid mixture flowsthrough the first channel 12 is maintained at a substantially constantrate throughout the first channel 12.

[0031] In contrast to the volume of the fluid mixture, the volumeoccupied by the fluid media effectively increases as the selectedspecies traverses the filtration membrane 30. This increase in volume iscompensated for by operation of the extraction pump 54 which withdrawsexcess fluid media, now containing the selected solute species, from thesystem 10. In this fashion, the selected species is removed from thefluid mixture and added to the fluid media. Generally, it may beappreciated that either the resulting fluid media (now carrying theselected species) or the fluid mixture (now stripped of the selectedspecies) may form the end-product of the filtration process.

[0032] A first alternate embodiment for the present invention is shownin FIG. 2. In FIG. 2, it may be seen that the system of the presentinvention includes all of the elements previously referred to in FIG. 1.In FIG. 2, however, an additional filtration membrane 30 a has beenadded. Filtration membrane 30 a is preferably of the same type and poresize as filtration membrane 30. Filtration membrane 30 a is alsopositioned in substantially the same location as filtration membrane 30.In effect, the combination of filtration membrane 30 and filtrationmembrane 30 a shown in FIG. 2 provides a double layer filter whichreplaces the single layer filter of FIG. 1 Functionally, inclusion ofone or more additional filter layers, such as filtration membrane 30 afunctions to prevent the minor filter defects associated with commercialgrade membrane filters from allowing non-selected species to traversefrom the first channel 12 to the second channel 14.

[0033] The system 10 shown in FIG. 1 as well as the alternate embodimentshown in FIG. 2 are adaptable for use in varying cascadedconfigurations. For example, in FIG. 3, the filtration system 10 of FIG.1 is replicated to form a two-stage, cascaded, configuration. In moredetail, FIG. 3 shows a first filtration system, generally designated 10,and a second filtration system, generally designated 10′. Both firstfiltration system 10 and second filtration system 10′ are fitted with aninput reservoir designated 60 and 60′ respectively. Additionally, theextraction pump 54 shown in FIG. 1, is omitted from system 10 and system10′.

[0034] Continuing with FIG. 3, it may be seen that the system 10 and thesystem 10′ are configured to continuously reprocess the fluid mixture.Therefore, mixture output conduit 44 is connected to reservoir 60.Likewise, mixture output conduit 44′ is connected to reservoir 60′. Thisallows the fluid mixture in system 10 and system 10′ to be continuouslyrecirculated through the respective first channel 12 and first channel12′. To cascade the filtration system 10 and the filtration system 10′the media output conduit 58′ is connected to reservoir 60 and the mediaoutput conduit 58 is connected to reservoir 60′. Preferably, the poresize chosen for filtration membrane 30′ is smaller than the pore sizechosen for filtration membrane 30.

[0035] The system 10 shown in FIG. 1 as well as the alternate embodimentshown in FIG. 2 are adaptable for use in multi-channel integratedsystems. For example, in FIG. 4, the basic filtration system 10 of FIG.1 has been replicated to form a multi-channel system 10″. Structurally,multi-channel system 10″ includes a first channel 62 and a last channel64. Between, first channel 62 and last channel 64, system 10″ includes aseries of intermediate channels 66 of which intermediate channels 66 aand 66 b are exemplary. Together, first channel 62, last channel 64 andintermediate channels 66 form a layered sequence of channels 68. Itshould be appreciated that the number of intermediate channels 66 isvariable to suit the ends to which a particular system is directed.Therefore, in FIG. 4, two intermediate channels are included while inFIG. 5, a configuration having only a single intermediate channel isshown. Within the layered sequence 68, first channel 62 and intermediatechannels 66 are configured as recirculating channels and have an inputend 70 and an output end 72. In comparison, last channel 64 isconfigured as a non-recirculating channel which lacks the input end 70and output end of first channel 62 and intermediate channels 66. Lastchannel 64 is, however, formed to include an output 74. Importantly, forthe purposes of the present invention, first channel 62 is formed to beconvergent between input end 70 and output end 72. It is to beappreciated that the convergent geometry shown for first channel 62 isthe same type of convergent geometry as used for first channel 12 ofsystem 10 shown in FIG. 1.

[0036] System 10″ also includes a series of filtration membranes 76 ofwhich membrane 76 a, 76 b and 76 c are exemplary. Each filtrationmembrane 76 is positioned to between a pair of channels within thelayered sequence of channels 68. For example, filtration membrane 76 ais positioned to separate first channel 62 and intermediate channel 66a. Likewise, filtration membrane 76 b is positioned to separateintermediate channel 66 a and intermediate channel 66 b. Each filtrationmembrane 76 is generally of the same type as filtration membrane 30shown in FIG. 1. For the purposes of multi-channel filtration system10″, however, each individual filtration membrane 76 is chosen to have aspecific pore size. Additionally, the filtration membranes 76 arearranged so that each successive filtration membrane 76 has a smallerpore size. In this fashion, filtration membrane 76 c has a smaller poresize than filtration membrane 76 b. Filtration membrane 76 b, in turn,has a pore size that is smaller than the pore size of filtrationmembrane 76 a.

[0037] System 10″ also includes a series of reservoirs 78 of whichreservoirs 78 a, 78 b and 78 c are exemplary, and a series ofrecirculation pumps 80 of which recirculation pump 80 a, 80 b and 80 care exemplary. As shown in FIG. 4, one recirculation pump 80 and onereservoir 78 are connected to recirculate fluid mixture between theoutput end 72 and input end 70 of the recirculating channels included inthe layered sequence of channels 68. For example, recirculation pump 80a and reservoir 78 a are connected between the output end 72 and theinput end 70 of first channel 62. Likewise, recirculation pump 80 b andreservoir 78 b are connected between the output end 72 and the input end70 of intermediate channel 66 a. In this fashion, each recirculationpump 80 and reservoir 78 operate to establish a recirculating flow offluid mixture from the input end 70 to the output end 72 of therecirculating channels included in the layered sequence of channels 68.

[0038] Continuing with FIG. 4, it may be seen that last channel 64 lacksthe recirculating flow of intermediate channels 66. In the case of lastchannel 64, however, it may be seen that output 74 is connected in fluidcommunication with reservoir 78 a.

[0039] In operation of system 10″, recirculation pumps 80 a andreservoirs 78 a continuously recirculate a fluid mixture through firstchannel 62. As the fluid mixture recirculates through first channel 62,fluid and species which are. not retained by the filtration membrane 76a pass through the filtration membrane 76 a and enter intermediatechannel 66 a. In this fashion, the fluid mixture recirculated throughfirst channel 62 becomes increasingly composed of those species that areretained by the filtration membrane 76 a.

[0040] Importantly, the convergent geometry of first channel 62compensates for the loss of the fluid volume of the fluid mixture due totraversal of fluid and species through the filtration membrane 76 a. Bycompensating for the loss of the fluid volume, the velocity at which thefluid mixture flows through the first channel 62 is maintained at asubstantially constant rate throughout the first channel 62.

[0041] In cooperation with the fluid mixture flow in first channel 62,recirculation pumps 80 and reservoirs 78 operate to continuouslyrecirculate fluid mixture through each intermediate channel 66. As thefluid mixture recirculates through each intermediate channel 66, fluidand species which are not retained by filtration membranes 76 leaveintermediate channel 66 and enter the next intermediate channel 66 orlast channel 64. In this fashion, the fluid mixture recirculated througheach intermediate channel 66 becomes increasingly composed of thosespecies that are retained by a particular filtration membrane 76. Theloss of fluid and species from each intermediate channel 66 is offset byan influx of fluid and species from the channel within the layeredsequence 68 which immediately precedes the particular intermediatechannel 66. In this fashion, the velocity at which the fluid mixtureflows through each intermediate channel 66 is maintained at asubstantially constant rate at all points within the intermediatechannels 66.

[0042] Effectively, then, operation of the system 10″ will act tostratify the fluid mixture, placing the largest species in first channel62, smaller species in intermediate channel 66 a and still smallerspecies in each subsequent intermediate channel 66. With the exceptionof the final filtration membrane within the layered sequence 68,recirculation pumps 80 preferably maintain the transmembrane pressureover each filtration membrane 76 at a value that lies between five andone-hundred percent (5-100%) of the transition point pressure (TPP) ofthe filtration process. As a result of the controlled transmembranepressure and the constant velocity of flow within each channel oflayered sequence 68, the ability of the multi-channel system 10″ toselect between similarly sized species is enhanced.

[0043] While the particular method and system for transferring aselected solute species from a fluid mixture to a fluid media as hereinshown and disclosed in detail is fully capable of obtaining the objectsand providing the advantages herein before stated, it is to beunderstood that it is merely illustrative of the presently preferredembodiments of the invention and that no limitations are intended to thedetails of construction or design herein shown other than as describedin the appended claims.

I claim:
 1. A . tangential-flow filter for selectively transferring aspecies from a fluid mixture to a fluid media, the filter comprising: afiltration membrane having a first surface and a second surface; acassette formed with a first channel and a second channel, the firstchannel being disposed to establish a tangential flow of the fluidmixture over the first surface of the membrane, the first channel havinga cross-sectional area with the cross-sectional area decreasing in thedirection of the tangential flow, the second channel being disposed toestablish a tangential flow of the fluid media over the second surfaceof the membrane; and means for creating a pressure differential betweenthe fluid mixture in the first channel and the fluid media in the secondchannel to cause the species to traverse the membrane from the fluidmixture to the fluid media.
 2. A tangential-flow filter as recited inclaim 1 further comprising one or more secondary filtration membranes,the secondary filtration membranes disposed between the first surface ofthe filtration membrane and the first channel.
 3. A tangential-flowfilter as recited in claim 1 wherein the first channel and the secondchannel are positioned side-by-side.
 4. A tangential-flow filter asrecited in claim 1 wherein the first channel and the second channel arepositioned coaxially.
 5. A tangential-flow filter as recited in claim 1wherein the velocity of the tangential flow of the fluid mixture issubstantially constant over the length of the first channel.
 6. Atangential-flow filter as recited in claim 1 wherein the pressuredifferential is maintained at a value which is less than the transitionpoint pressure (TPP) of the tangential-flow filter.
 7. A tangential-flowfilter as recited in claim 1 wherein the decrease in the cross-sectionalarea in the direction of the tangential flow is chosen so that thepressure differential is substantially constant over the length of thefiltration membrane.
 8. A tangential-flow filter as recited in claim 1wherein the decrease in the cross-sectional area in the direction of thetangential flow is chosen to compensate for volumetric changes to thefluid mixture caused by the traversal of the filtration membrane by thespecies.
 9. A tangential-flow filter as recited in claim 1 wherein thefiltration membrane is chosen to selectively pass species having amolecular weight of approximately 1 to 1000 kDa.
 10. A tangential-flowfiltration apparatus separating a fluid mixture into species of interestcomprising: a cassette formed with a layered sequence of side-by-sidechannels including a convergent first channel and a last channel, theconvergent first channel and at least one intermediate channelconfigured as recirculating channels having an inlet and an outlet, thelast channel configured as a non-recirculating channel having an outlet;a series of filtration membranes, one filtration membrane positionedbetween each successive pair of channels in the layered sequence witheach successive pair of channels in the layered sequence being separatedby a filtration membrane having a successively smaller pore size; meansfor creating a flow of the fluid mixture between the inlet and theoutlet of each recirculating channel; and means for creating a pressuredifferential between each successive pair of channels in the layeredsequence.
 11. A tangential-flow filtration apparatus as recited in claim10 wherein the cassette is formed to include one intermediate channel.12. A tangential-flow filtration apparatus as recited in claim 10wherein the cassette is formed to include two intermediate channels. 13.A tangential-flow filtration apparatus as recited in claim 10 whereinthe outlet of each recirculating channel is connected in fluidcommunication to the inlet of the channel.
 14. A tangential-flow filteras recited in claim 10 wherein the velocity of the flow of the fluidmixture is substantially constant within each recirculating channel. 15.A tangential-flow filter as recited in claim 10 wherein the pressuredifferential between each successive pair of recirculating channels inthe layered. sequence is maintained at a value which is less than thetransition point pressure (TPP) of the tangential-flow filter.
 16. Atangential-flow filter as recited in claim 10 wherein the convergentfirst channel is dimensioned so that the pressure differential betweenthe convergent first channel and the intermediate channel issubstantially constant over the length of the filtration membranepositioned between the convergent first channel and the intermediatechannel by the species.
 17. A tangential-flow filter as recited in claim10 wherein the convergent first channel is dimensioned to compensate forvolumetric changes to the fluid mixture caused by the traversal of thefiltration membrane positioned between the convergent first channel andthe intermediate channel by the species.
 18. A process for selectivelytransferring a species from a fluid mixture, comprising the steps of:passing the fluid mixture through a channel for tangential flow over afirst surface of a primary filtration membrane, the channel shaped tohave a cross-sectional area, the cross-sectional area decreasing in thedirection of the tangential flow; passing a fluid media for tangentialflow over a second surface of the primary filtration membrane, thetangential flow of the fluid mixture adjacent to the tangential flow ofthe fluid media; and creating a pressure differential between the fluidmixture in the channel and the fluid media to cause the species totraverse the primary filtration membrane from the fluid mixture to thefluid media.
 19. A process as recited in claim 18 further comprising thestep of filtering the fluid media by tangential flow filtration over asecondary filtration membrane, the secondary filtration membrane havinga smaller pore size.
 20. A tangential-flow filter for selectivelytransferring a species from a fluid mixture to a fluid media, the filtercomprising: filtration means having a first surface and a secondsurface; channeling means for causing the mixture to flow tangentiallyat a first pressure over the first surface of the filtration means, thechanneling means having a length, the channeling means shaped todecrease from a first cross-sectional area to a second cross-sectionalarea over the length of the channeling means; means for causing thefluid media to flow tangentially at a second pressure over the secondsurface of the filtration means, the first pressure and the secondpressure creating a pressure differential over the filtration means, thepressure differential causing the species to traverse the filtrationmeans from the fluid mixture to the fluid media; means for creating apressure differential between the mixture and the fluid media, thepressure differential causing the species to traverse the filtrationmeans from the fluid mixture to the fluid media.
 21. A tangential-flowfilter as recited in claim 20 wherein the filtration means comprises afiltration membrane.
 22. A tangential-flow filter as recited in claim 20wherein the filtration means comprises a plurality of filtrationmembranes.
 23. A tangential-flow filter as recited in claim 21 whereinthe first cross-sectional area and the second cross-sectional area arechosen so that the decrease of cross-sectional area compensates forvolumetric changes to the fluid mixture caused by the traversal of themembrane by the species.
 24. A tangential-flow filter as recited inclaim 21 wherein tangential flow of the fluid mixture is substantiallyconstant over the length of the channeling means.
 25. A tangential-flowfilter as recited in claim 21 wherein the first area and the second areaare chosen so that the pressure differential is substantially constantover the length of the channeling means.
 26. A tangential-flow filter asrecited in claim 20 wherein the filtration means is chosen toselectively pass species having a molecular weight of approximately 1 to1000 kDa.